Hyperthermia, or the use of elevated temperatures to repress tumors, has been known and studied for many years.
Many cancerous tumors embedded in healthy human tissue have well-defined boundaries and tend to be irreversibly damaged by hyperthermia. Tumor temperature elevation to 43.degree.-46.degree. C. for 90 to 120 minutes appears to be sufficient to kill many types of malignant growths. Several systems for generating and delivering heat to these localized tumors have been proposed. They include capacitive and inductive RF systems, use of a single microwave source, focused ultrasound systems, invasive electromagnetic probes, and microwave heating arrays. Much of the current interest is directed to non-invasive sources, which are less traumatic to sick patients and minimize the risk of mixing abnormal cells into healthy tissue.
External applicators are also more flexible than invasive ones It is possible for many of these applicators to be reconfigured to suit the requirements of a particular case. Also, a non-invasive applicator can be designed to surround the body part containing the tumor, taking advantage of constructive interference and focussing to concentrate more heat at the tumor than in the surrounding normal tissue.
The two broad classes of external hyperthermia applicators are electromagnetic (EM) and ultrasound (US). Electromagnetic applicators radiate waves which propagate at the speed of light, 300,000 km/sec in vacuum, or slower in matter, and are characterized by both a propagation direction, and a vector polarization. Ultrasound is an acoustic wave which cannot propagate in a vacuum, has a much slower velocity (about 1500 m/sec in soft biological tissue), and; since it is a compressional wave, does not have a polarization attribute.
As a wave propagates through a dissipative (lossy) medium, it attenuates as it deposits power, in the form of heat, in the medium. The attenuation rate is exponential, represented by e.sup.-.alpha.x, where x is depth into the medium and .alpha. is the attenuation rate. Since the attenuation rate varies directly with frequency, radiation at higher frequency penetrates less deeply than a lower frequency.
The spatially oscillatory nature of waves is described by the relation cos.beta.x, where .beta.=2.pi./.lambda. is the propagation constant, inversely proportional to wavelength. Any spatial features, such as peaks or troughs, will extend for a distance on the order of a wavelength. A major distinction between EM and US radiation is the much greater resolution and focussing ability of the latter. Since US propagation velocity is 200,000 times slower than that of EM, the propagation constant .beta. is much bigger for a given attenuation constant .alpha..
The entire spatial behavior of either type of wave is governed by the .alpha. and .beta. parameters. A convenient representation in terms of the complex wave number is: EQU k=.beta.-j.alpha.
The optimal non-invasive applicator delivers maximum power to the tumor while minimally heating surrounding healthy tissue. Since waves attenuate as they penetrate lossy tissue, a focussing source arrangement is required. Constructive interference at the tumor is obtained by adjusting the phase and amplitude of each point of the source. Unlike in free space, nearfield focussing in a lossy medium is more involved than simply compensating for the path length variations from tumor to source. Also, since the attenuation rate varies directly (though non-linearly) with frequency, while field resolution decreases with decreasing frequency, any attainable "focus" is relatively wide and of low intensity. The broadening and smearing of this focal maximum increases as the physical distance in the medium to the source increases, until the exponential decay overwhelms any geometrical focussing advantages. For heating a tumor in the center of a volume of tissue, the best range of frequencies is found by choosing those patterns of dissipated power (if any exist) that have the same or greater power at the focus as at the tissue surface with lower power for all intervening tissue, including muscle/fat boundaries. Generally, the sharpest focus or highest resolution will correspond to the highest possible frequency within this range of frequencies. Exceeding this range may produce higher resolution, but the actual penetration depth into the tissue will decrease.
More complicated than frequency selection is the determination of optimal source distribution. Unlike with the acoustic compression waves of ultrasound hyperthermia, electromagnetic waves incorporate polarization. For constructive interference at a focus, electric field at the tissue surface must be properly aligned and phased so that waves propagating along all paths in the entire tissue volume arrive in the same fashion. However, merely adjusting phase, polarization, and also amplitude for maximum focussing does not necessarily produce an acceptable power-density distribution.
Several experimental means of determining source distribution have been proposed. These include passive methods, such as remote sensing and active methods, such as invasive implantation of a small source at the intended focus and subsequent phase measurement at the surface and inversion for source specification. Both methods overlook the difficulty of undesirable hot spots or excessive surface heating. Correcting the source distributions to prevent this often eliminates any geometrical advantage at the focus.
One further requirement of applicators is a method of monitoring power deposited in the exposed tissue. Applied dosage information may be used as an approximate substitute for the difficult problem of direct non-invasive temperature measurement.
Although the effects of phase focussing a wave in tissue is not as great as in free space, advantage can be taken of a finite tissue volume by surrounding it with applicator sources. Two main simplified cases that yield good power patterns have been examined. (See Rappaport, Cary M. and Morgenthaler F. R., "Localized Hyperthermia with Electromagnetic Arrays and the Leaky-Wave Troughguide Applicator", IEEE Transactions on Microwave Theory and Techniques, Vol. MTT-34, No. 5, May 1986.) The first case is that of planar arrays facing each other and the second case involves cylindrical arrays. In the above-referenced article, a troughguide leaky-wave antenna hyperthermia applicator was described which can be configured as either a planar array source or cylindrical array.
A leaky-wave antenna guides a controlled amount of power down its length. Boundary conditions for the interior propagating guided field at the opening are satisfied by a tangential E-field. Since the interior guided field propagates down the guide, the tangential E-field across the opening must have progressive linear phase. Thus, a non-uniform plane wave radiates at the angle .theta. from broadside specified by EQU .theta.=sin.sup.-1 (.lambda..sub.o /.lambda..sub.g)
where .lambda..sub.o and .lambda..sub.g are the free-space and guide wavelengths, respectively.
The asymmetric troughguide is a leaky-wave antenna consisting of a U-shaped channel, open at one side, with a center fin attached to its base and running down its length. The base on one side of the central fin is raised, introducing the asymmetry that generates a tangential E-field across the open top. A wide range of amplitude control is available by adjusting the relative height of the bases on each side of the fin. Reversing the asymmetry reverses the field, causing a 180.degree. phase shift at the aperture.
One of the advantages of the trough guide is the ready availability of power monitoring. Using short probes mounted at the points of high guide-E-field along the side wall and small loops along the base where H-field is strongest, these field quantities can be measured. Knowledge of both components is essential to avoid standing-wave ambiguities caused by reflections. With knowledge of the power as a function of distance within the guide, the radiated power between any two points is available. Since reflections are already taken into account with this monitoring, the measured radiated power is the actual power entering the exposed tissue.